PROJECT SUMMARY: The proposed research aims to convincingly establish new physically-grounded non- invasive techniques to quantify the severity of intra-articular fractures. Post-traumatic osteoarthritis (PTOA) is a frequent and often early complication of treatment, with substantial lifelong morbidity and disability. The intensity of the initial joint trauma in intra-articular fractures is a critically important factor in the etiology of PTOA. Interventions to surgically reduce the displaced and fragmented articular surface have been developed and refined over decades. Yet, for some injuries, PTOA remains seemingly inevitable, with surgical advances unlikely to appreciably change the prognosis. Little is known regarding the biological processes at work within the joint shortly following these injuries, or how they link joint injury to eventual PTOA. Newly proposed biologic interventions warrant further scientific evaluation, but this will require that patient cohorts be reasonably stratified and studied in large enough numbers to yield statistically robust findings. To stratify patients, the severity of the initial injury must be objectively measured, lest it remain a substantial confounder that will continue to preclude meaningful investigation. We have developed and validated enabling technology to measure fracture severity in a clinical setting. AIM 1: We will extend and expedite this CT-based methodology to better assess articular fractures, implementing new techniques to assess articular fragmentation, fragment dispersal, and the soft tissue injury. AIM 2: In a prospective multi- center study we will correlate the expedited injury severity metric with a new computer-based method to continually rank order cases for severity, and we will correlate both of these severity metrics with the development of PTOA. AIM 3: We will assay synovial fluid from injured ankles in a prospective study of tibial plafond fracture patients, to gather descriptive data regarding joint damage and recovery in the early post- injury period. These biologic markers will be correlated with the expedited injury severity metric, and each in turn will be correlated with patient outcomes. RELEVANCE TO PUBLIC HEALTH: Patients who sustain fractures that extend into an articular joint, such as the ankle or knee, have a generally poor prognosis, with eventual arthritis as a common disabling result. Surgeons rely upon subjective empirical experience to guide articular fracture treatment, and this greatly hinders progress. This study will provide fundamentally new objective non-invasive methods to measure articular fracture injury severity. These methods will have important clinical implications in their own right, and provide a novel framework for statistically robust clinical/translational studies to reduce the risk of PTOA.